Good morning, ladies and gentlemen, and welcome to the Altimmune third quarter 2026 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. As a reminder, this call is being recorded. I will now introduce your host for today's conference call, Luis Sanay, Vice President of Investor Relations. Luis, you may begin.
Thank you, operator, and good morning, everyone. Thank you for joining us for Altimmune's third quarter 2026 financial results and business update call. On today's call, you will hear from Jerry Durso, our Chairman and Chief Executive Officer, Dr. Christophe Arbet-Engels, Chief Medical Officer, Linda Richardson, Chief Commercial Officer, and Greg Weaver, Chief Financial Officer. Following management's prepared remarks, we will open the line for questions. Our third quarter 2026 earnings release was issued this morning and can be found on the Investor Relations section of our website. Before we begin, I would like to remind everyone that remarks made about future expectations, plans, and prospects constitute forward-looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated.
For a review of the risk factors that could affect the company's future results and operations, we refer you to our SEC filings. I also direct you to read the forward-looking statements disclaimer in our press release issued this morning. Any statements made on this call speak only as of today's date, November 12, 2026, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this call is being recorded and will be available for audio replay on our website. With that, I will now turn the call over to Jerry.
Good morning, everyone, and thank you for joining us today. We enter the final months of the year with strong confidence in pemvidutide and the strategy we are laser-focused on executing. Over the course of this year, we significantly advanced our programs across the board in MASH, AUD, and ALD, further strengthening our belief that pemvidutide's differentiated clinical profile can support a broad liver franchise with multiple indications in serious liver diseases. We are now focused on carrying that momentum forward through disciplined execution. We continue to see a growing understanding and scientific support for the potential therapeutic role of Pemvi and its ability to provide meaningful benefit to people affected by serious liver diseases. Our conviction in pemvidutide is stronger than ever coming out of AASLD's The Liver Meeting, where the data presented further validates the potential of pemvidutide and our overall development strategy.
MASH data presented at several podium talks at the meeting reinforced the potential of the dual glucagon GLP-1 mechanism in MASH and underscored the differentiation of pemvidutide. We presented new NIT data from our 48-week IMPACT study that highlighted the strong anti-fibrotic activity of Pemvi that continues to compare favorably to data across other trials. We believe pemvidutide's balanced 1:1 glucagon to GLP-1 ratio, when coupled with our proprietary EuPort domain, matters and results in a molecule that balances metabolic and liver-directed activity with generally favorable tolerability. Despite new products entering the MASH field and others in various stages of development, there remains a significant unmet need for patients, and we believe that pemvidutide could represent a well-differentiated MASH therapy. We see a major commercial opportunity across the indications we're targeting as we build our liver franchise.
In addition to the unmet need in MASH, we view AUD and ALD as part of a patient continuum, as AUD patients often progress to liver impairment. In fact, data referenced at The Liver Meeting estimates that 55%-94% of ALD patients also meet the criteria for AUD. The RECLAIM data highlighted that Pemvi has the potential to help address both alcohol consumption and the liver damage that can result from it. Finally, one of the recurring themes at The Liver Meeting was about the overlap of MASH and alcohol use. We believe pemvidutide's differentiated profile positions it well across a multitude of patients. Moving now on to execution, which is a critical focus for Altimmune. First, our global PERFORMA phase III trial is ramping up, and we're very encouraged by the progress to date.
Clinical trial sites continue to come online according to our plan, and we're actively enrolling patients. The engagement we see from the PERFORMA investigators and the broader MASH community is strong. This excitement was quite evident at The Liver Meeting, and Christophe will touch on the positive feedback and engagement from KOLs on PERFORMA and pemvidutide overall. We're also pleased that the IMPACT phase IIb 48-week efficacy and safety data was published in The Lancet this week. In AUD, the positive RECLAIM phase II data were highlighted in a late-breaking oral presentation. We believe this is the most robust AUD data presented to date. The strong results we saw significantly de-risk this program. Importantly, our end-of-phase II meeting with the FDA is scheduled for next month, representing a key step towards advancing pemvidutide in AUD.
We look forward to engaging with the agency and continuing our progress of Pemvi in this indication. As part of our continued evolution as a late-stage biotech company, we're also thrilled to recently have added Peter Greenleaf and Alex Howarth to our board of directors. Peter and Alex are accomplished industry leaders that bring a breadth of experience across drug development, commercialization, and corporate development. Their experience and strategic perspectives will be valuable to Altimmune as we continue to advance.
In summary, we're committed to executing our strategy with speed and efficiency reflected in the significant progress we've made across the pemvidutide franchise this year. We're laser-focused on delivering on our goals of bringing a differentiated therapy in Pemvi to patients and creating value for our shareholders. Our conviction in pemvidutide is stronger than ever, and we look forward to sharing our continued progress. I'll now turn the call over to Christophe for a clinical update.
Thank you, Jerry. I'd like to start by just stating that I am very pleased with the significant progress we are making as we advance our clinical programs across MASH, AUD, and ALD. Beginning with MASH, the global PERFORMA phase III trial is underway and progressing as planned. We are screening and dosing patients, and clinical site activation continues across the program as we build towards broader global enrollment. We have the majority of planned U.S. sites now active and recruiting patients, and we expect to activate the ex-U.S. sites over the coming months. We will continue to work closely with our CRO partner to support efficient trial execution and enrollment. Overall, we remain encouraged by the enthusiasm and engagement we are seeing from investigators and clinical sites for PERFORMA based on the product profile and the efficient trial design.
As a reminder, we anticipated the PERFORMA 52-week data readout in 2029. Altimmune had a strong presence at the recent Liver Meeting in Denver, where we had the opportunity to highlight the potential of pemvidutide in serious liver diseases. We saw a growing interest and excitement for pemvidutide from the scientific community and the role it may play in treating the liver damage that characterizes the overlapping metabolic and alcohol-associated diseases of MASH, AUD, and ALD. During the Liver Meeting, we presented two analyses from the IMPACT phase IIb trial, including compelling data showing concurrent improvement across multiple non-invasive measures of liver fat, inflammation, and fibrosis compared to patients receiving placebo. The new data further illustrate the strong and consistent anti-fibrotic activity and a generally favorable tolerability profile in the absence of dose titration.
Our data, along with emerging data from other glucagon GLP-1 programs, reinforce the importance of glucagon in treating MASH. The totality of our learning during the Liver Meeting further support our phase III study design. We also hosted a well-attended disease state product theater where Dr. Mazen Noureddin, Dr. Rohit Loomba, and Dr. Jessica Mellinger discussed the advanced liver disease continuum. They noted the prognostic importance of fibrosis on outcomes and how various factors, including alcohol consumption or metabolic dysfunction, impact the progression of serious liver disease. The product theater further underscored the overlap between excessive alcohol consumption and metabolic causes of serious liver disease and the high unmet need for a therapy that can chronically address both causes and their liver damage consequences.
We believe that the data presented on pemvidutide during The Liver Meeting strongly support the potential of pemvidutide to address that unmet need with a generally well-tolerated approach that is particularly suitable for chronic diseases such as MASH, AUD, and ALD. In addition, Dr. Henry Kranzler, the lead investigator for our RECLAIM phase II trial, presented the very robust and positive study results in the late-breaking oral presentation at The Liver Meeting. To our knowledge, the RECLAIM data is the strongest data in AUD to date. The trial showed statistically significant improvements with pemvidutide across the primary endpoint of heavy drinking days, as well as key secondary measures, including WHO-RDL and achievement of zero heavy drinking days, both of which are FDA registrational endpoints. Importantly, we also demonstrated that PEth, an objective serum-based measure of alcohol consumption, corroborated the self-reported reduction in alcohol intake in Pemvi-treated patients.
Pemvidutide also increased abstinence in patients with AUD. While RECLAIM was focused on drinking behaviors, the trial demonstrated in an exploratory analysis that Pemvi decreased the proportion of patients with elevated risk for developing advanced liver fibrosis as measured by FIB-4. These data point towards potential liver improvement in this patient population. Given Pemvi's direct glucagon effect on the liver, the observed data is very encouraging, and we expect to further evaluate the potential liver benefits in the registrational phase III study in AUD, with inclusion of a subpopulation of AUD patients with advanced liver impairment. Importantly, RECLAIM was conducted in patients with moderate to severe AUD, the population we believe may have the greatest need for more effective and safe treatment options, and who are at risk of alcohol-related liver disease.
The overall strong positive results, including the generally favorable safety profile observed in the trial, positions us well to engaging with regulatory agencies to align on the next steps for the program. To that end, our end-of-phase II meeting with the FDA is scheduled for December, where we expect to discuss the study design and regulatory path for a phase III AUD program. Typically, meeting minutes follow within 30 days. In our registrational program, we will focus on moderate to severe patients, including a subpopulation of patients with advanced liver impairments such as ALD. This approach not only aligns with FDA guidance, where patients with hepatic impairment should be enrolled in AUD registration programs, but also may address the current unmet need, as therapies for AUD are not specifically indicated in the hepatically impaired subpopulation.
In terms of trial design, we expect the primary endpoint to be the WHO-RDL, with no heavy drinking days as a key secondary endpoint, both of which reached statistical significance in the RECLAIM phase II trial. We expect other secondary exploratory endpoints to include additional self-reported drinking endpoints, PEth, body weight, and liver endpoints, including liver fat content, liver stiffness measurements, and ELF. We would look to include both 1.8 milligram and 2.4 milligram doses with a simple one to two-step titration. The proposed trial will have a primary efficacy read at 26 weeks and continue up to one year for additional safety and efficacy data. The final program design will, of course, be subject to our dialogue with regulators. Moving now to ALD. The RESTORE trial enrolled 121 patients with ALD and a history of chronic and heavy drinking at baseline.
The 48-week trial is designed to demonstrate the liver benefits over a period of 48 weeks and includes additional evaluations at 24 weeks. Given the significant overlap between the ALD and AUD patient population, demonstrating liver benefits in the RESTORE trial could further support a unique role for pemvidutide in decreasing both chronic alcohol consumption and the liver damage it causes. We also believe that the ALD RESTORE trial will further strengthen our filing package and discussion with regulator when seeking an AUD indication.
We expect the top-line data for RESTORE in the second half of 2027. In summary, the significant progress achieved during 2026 across all our clinical program positions Altimmune well heading into 2027. I echo Jerry's sentiment that our conviction in pemvidutide is stronger than ever. We look forward to executing against the key clinical and regulatory milestones ahead, moving us closer to bringing pemvidutide to patients. With that, I will turn the call over to Linda.
Thanks, Christophe. Good morning, everyone, and thank you for joining us today. Following the conclusion of The Liver Meeting 2026, I would like to reflect on why we believe pemvidutide remains well-positioned in the MASH and AUD markets as a differentiated potential future therapy. First, new data presented at The Liver Meeting clearly supports the validity of the dual glucagon GLP-1 mechanism of action in the treatment of MASH. That said, the molecule matters, as we see different profiles emerging within the glucagon GLP-1 class. Pemvidutide's balanced 1:1 glucagon GLP-1 ratio has already shown significant early improvements in MASH resolution in our phase IIb IMPACT study, and strong data on fibrosis improvements based on 24 and 48-week NIT analyses.
In addition to the strong profile of the 1.8 milligram dose we saw in phase II, the 2.4 milligram dose now being studied in our 52-week PERFORMA phase III MASH trial may offer additional upside in terms of weight loss and efficacy. Our generally favorable tolerability profile, seen now across multiple pemvidutide trials, and lack of significant drug-drug interactions, are important product features that should help patients remain on Pemvi therapy, as well as continue medications they may be taking for comorbid conditions. These two specific features, in addition to our dual mechanism of action, suggest that Pemvi may play an important future role as a potential combination therapy for MASH patients who do not reach therapeutic goals or cannot tolerate their current therapy. Second, despite the availability of approved therapies in MASH, one thing remains clear. A significant unmet need remains.
While encouraged by the growth seen to date in the MASH market, diagnosis and treatment rates remain low, but we expect this dynamic to evolve. We also believe that evaluating MASH treatment options for patients will move beyond focusing primarily on diabetes and obesity comorbidities to also address additional NITs. For example, patients diagnosed with MASH who also drink, those who are at risk for sarcopenia and need to preserve lean muscle mass, and post-menopausal women facing decreases in bone mineral density may be important patient segments for pemvidutide in the future. Third, with Pemvi, we have a significant opportunity to potentially redefine what to expect from drug therapy in alcohol use disorder based on our specific profile of reducing alcohol consumption and perhaps demonstrating direct improvements on the liver, given our glucagon activity. This could subsequently help activate one of the largest underserved markets in the U.S.
As a reminder, approximately 27 million Americans meet the criteria for AUD, and 12 million of these patients are believed to have moderate to severe AUD. This more advanced segment has the highest risk of progressing to severe liver damage and is where pemvidutide's dual mechanism of action may be most compelling. Christophe highlighted our AUD data from RECLAIM earlier in the call, but I would like to also note that our early mover status in AUD is a competitive advantage for Pemvi, as we are generating important new data in this field.
Pemvi's balanced 1:1 glucagon GLP-1 ratio, providing both metabolic and direct liver benefits, generally favorable tolerability profile, lack of significant drug-drug interactions, and simple patient-friendly dosing drives significant differentiation versus other therapies in development across MASH, AUD, and ALD. We are excited about Pemvi's potential, confident in our existing data, and look forward to sharing additional insights on future calls. Greg, you will now share our financials for the third quarter.
Thank you, Linda, and good morning. Beginning with our financial results for the quarter, R&D expense in Q3 2026 totaled $27 million, compared to $15 million for the same period prior year. The year-over-year increase in R&D spend is primarily driven by the initiation of the phase III trial in MASH and the ongoing phase II trial in ALD. Q3 2026 R&D spend included $20.3 million of direct costs related to pemvidutide development, of which $10.7 million was for MASH, $4.3 million for the phase II ALD and AUD trials, and $5.4 million in CMC-related expenses. Q3 2026 R&D also included $1.1 million in non-cash stock compensation. G&A expenses in Q3 2026 were $8.7 million, compared to $5.9 million for the same period prior year, as we added additional talent to the company. The increase in G&A was driven by the increase in compensation expenses and professional fees.
Q3 2026 G&A included $1.8 million in non-cash stock comp. The net loss for the third quarter of 2026 was $31.6 million, or $0.15 a share, compared to a net loss of $19 million, or $0.21 a share, in the third quarter of 2025. Now moving to the balance sheet, we ended the quarter with $480 million in cash equivalents, and investments. Our year-to-date cash burn tracks in line with plan and is expected to provide operating runway through the PERFORMA phase III MASH 52-week data readout expected in 2029.
In addition, following upcoming regulatory feedback in AUD, we expect to have greater clarity on the scope and investment required for a phase III program in AUD. Our preference remains to pursue non-dilutive funding for the program, including potential royalty debt or strategic partnership opportunities. Thank you very much. That concludes prepared remarks. I now turn the call back to the operator for the Q&A session. Operator?
Thank you, sir. As a reminder, to ask a question, you need to press star 11 on your telephone. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Thomas Smith from Leerink Partners. Please go ahead.
Hey, guys. Good morning. Congrats on all the progress, and thanks for taking our questions. On PERFORMA, I know you've talked about enrollment timelines in the 18 to 24-month ballpark. Just wondering if you could provide an update on how you're tracking here in the early days relative to that timeline, and what aspects of the trial design you think will drive preferential enrollment over some of the competing phase II or phase III programs?
Okay. Thanks for the question, Tom. Good to speak to you. I'll start, and then Christophe can add in. As a reminder, our current guidance calls for a readout of PERFORMA in 2029. As you mentioned, we've been discussing this 18- to 24-month range in terms of the time we think enrollment will take. We are really encouraged on what we're seeing in the early ramp-up as we really focus on site activation. At this point in the study, it is the lead indicator, while we also begin to enroll and dose patients. Christophe mentioned in the prepared remarks that the initial focus, as is typical, has been on the U.S. sites.
We already have over 70 U.S. sites activated, and we now anticipate in the next period that will also commence on the ex-U.S. sites, which take a little bit of time for some of the work that has to happen country by country. So we'll look to communicate on-site activations periodically as we progress, and then we'll provide other appropriate updates as the study matures. The second part of your question, Thomas, was around some of the elements happening to make enrollment happen in a strong way, and I think we already have some good insight from the sites, maybe Christophe, that you can talk about a little bit.
Yeah, absolutely. So we are early into the study, but we are very encouraged by what we're seeing, the enthusiasm from the sites, the study design, how it is set up, how we plan the interactions with sites is making it very attractive for those PI to enroll their patients. So, as Jerry said, activation of sites is, with our more than 70 sites in the U.S., is happening, and we're really happy it's on plan, tracking on plan. Then in the next few weeks or months, we're going to start getting the ex-U.S. As you know, these take time a little more. But the enthusiasm that we've seen, whether in investigator meetings or at AASLD, was substantial and really encouraging.
That's great. Super helpful. Just a follow-up if I could. I know at The Liver Meeting, Merck also presented some phase IIb MASH data for their GLP-1 glucagon agonists that included some histology data at 52 weeks. Also included semaglutide active comparator arm. Just wondering if you could comment on that dataset and what you saw in the profile there relative to Pemvi, and any potential learnings or read-throughs from that study as it relates to PERFORMA? Thanks so much.
Yeah. I think, look, we were interested in the data, of course. We think that that dataset further validates the mechanism. Christophe can talk a little deeper, probably gives us a good indicator that 12 months is a good time to read the biopsy, which is what we deployed in PERFORMA. I also think that, again, the totality of the picture we've seen, we believe that pemvidutide compares favorably and offers some advantages to patients. That will be a big part of what we continue to speak about and to focus on, because the differentiation from the other options is going to be key.
Yeah. No, and exactly. This is what we observed with the efinopegdutide data, and again, it is two separate studies, not a head-to-head comparison. But the fact that they demonstrated with that open-label GLP-1 arm added value of the glucagon component from the GLP-1 is, for us, really important. It is now the third or fourth dual agonist also that validates the mechanism, that class. We like what we see with pemvidutide, that tolerability, the strong efficacy at our 1.8 milligram dose. We will test also the 2.4 milligram dose in our phase III PERFORMA trial. So this actually comforts us in our assumptions for the phase III trials and the probability of success for it.
Got it. That is helpful. Thank you, guys.
Thanks, Thomas.
Thank you.
Thank you. Our next question comes from the line of Michael DiFiore from Evercore. Please go ahead.
Hi, guys. Thanks so much for taking my question. Two for me. One on PERFORMA. Not sure if you disclosed in the past, but what placebo rate and treatment effect did you assume for PERFORMA's fibrosis endpoint, and how does that compare with IMPACT? Then separately, for AUD, now that the phase II RECLAIM data have been out for a while, was wondering if the drug-related discontinuations cluster around the step-up to 2.4 milligrams, and does that change how you're thinking about titration in PERFORMA? Thank you.
All right. First, on the PERFORMA, the placebo rates, we've taken, as we've shared, we haven't disclosed the whole statistical details, but as we've shared, we have taken a very conservative approach that is based on what other trials have achieved so far for approved drugs. Now, having said this, as you remember, and as the recent article manuscript that has been published on our 48-week data, our needs were much stronger than this. But given the size of the study and the way to develop such a study, we have to take those assumptions into consideration.
Regarding the placebo, again, a couple of things. We have probably the most robust approach with regard to the biopsy reads. We've reconfirmed this through AASLD. The part that is important is this AIM-MASH AI Assist as well, the selection of the pathologist. The AIM-MASH AI Assist is something that clearly increased precision, accuracy, and decreased variability on the biopsy reads. These are important factors, and that will be playing in our favor if this pan out to be really the case here. On the AUD side, could you repeat the questions?
Sure. Now that the full phase II RECLAIM data are out, did the drug-related discontinuations cluster around the step-up to 2.4 milligrams? If so, does that change how you're thinking about titration in the phase III PERFORMA MASH trial? Thank you.
No. That doesn't change anything on the phase III PERFORMA MASH trial. Actually, it comforts us. These are two different populations, so we have to be very careful. A couple of learnings here. One, the profile of those AE is not unexpected, and there's nothing new there. The second is, in different population, you may see some variability in those AE profile, but clearly in our AUD, the titration for monthly of one step or two step, because in our phase III, we will go also with the 1.8 milligram dose that was extremely well tolerated in the phase II MASH trials. Putting this together, we're comfortable moving forwards and confidence that we can manage and keep the very good tolerability profile that we've seen with pemvidutide throughout different populations.
Great. Thanks so much.
Thank you.
Thanks, Michael.
Thank you. Our next question comes from the line of Ellie Merle from Barclays. Please go ahead.
Good morning, Ellie.
Hi, this is Joseph Ong for Ellie. Thanks for taking our question. Congrats on the progress. For AUD, could you remind us of the percentage of AUD patients who have obesity, diabetes, and MASH, and if there's any real-world evidence from off-label GLP-1 use in AUD?
The percentage of patients with AUD in MASH is actually looked at under the umbrella of the MetALD patients. We know that there is more than 10% of this population. Keep in mind that this is not always screened appropriately, that the test, evaluation test is not always done. It's probably very much underestimated, and actually at the AASLD, again, at the Liver Forum, there was a clear overlap between the patients that do have MASH and the patients that do have alcohol, and these diseases are very much related.
The other things that I wanted to mention is, what we know is that on the ALD side, they're close to 55%-94%, so almost all of them that do have AUD. There is clearly two aspects to consider. There is the liver damage in itself, which is at the center of these two different pathologies, and there's the different causes, and these seem to have more and more overlap as we learn more about these different patients' populations.
I think the role of obesity also is you clearly see that as a comorbidity in MASH, but you also have calories from drinking, et cetera. These patients may also be obese and drinking and have MASH. In ALD, sometimes this dynamic changes because you can have the lean drinking, they're drinking, they're not consuming calories. There is a spectrum with the weight across both MASH, AUD, and ALD, different concerns. Clearly, the lean muscle mass sparing elements potentially of our drug will be important in all the populations.
And one quick follow-up, if I can. When can we expect an update on AUD from your learnings from the end of phase II meeting with FDA?
So, as we announced, we're going to have that meeting in December. You typically anticipate the minutes coming within 30 days after that, and we would communicate appropriately at that point. As you would expect.
Thank you.
We also anticipate dialogue, as Christophe mentioned, with EMA happening in the first quarter.
Thank you. Our next question in the queue comes from the line of Kripa Devarakonda from Truist. Please go ahead.
Hi, this is Alex on for Kripa. Question from us. Can you provide an update on how you are thinking about a potential partnering or the lack thereof in order to optimize the development of Pemvi across all three indications? If you could provide more detail on how, when, or if you would pursue a partnership, and what would Altimmune be looking for in a partner if they did choose to go that route? Thanks.
As you can imagine, as our program matures, we are active on this front and fully open to approaches that help move Pemvi forward and create value. As Greg said, in the context of the non-dilutive options that we would prefer to fund AUD, that is one of them. I cannot go into any more detail than that, but that is how we think about it strategically, while we ensure that we are driving execution on our program as strongly as possible.
All right. Thanks, Jerry. Congrats on the progress.
Thank you.
Thank you. Our next question comes from the line of Catherine Okoukoni from Citizens. Please go ahead.
Hi, this is Catherine on for John Wolleben. I just have a quick question on developmental timelines. How are you thinking about prioritizing? I know the meeting's clear up a lot of the phase III design AUD, but as far as prioritizing the start of the phase III, what variables are going to determine that, and any more commentary on how you guys are thinking about developmental timing? Thank you.
Yeah, I think as we have been indicating, the next step in this process is that feedback that we'll solicit and discuss with the agency in December. That will allow us to take that important input around sizing and scoping the trial. We will be getting feedback from Europe alongside of that. As we said, then the opportunity of ensuring that we're building towards the right kind of value-creating funding will be happening. So we're not at a point where we're going to guide specifically on timing, but we think about this in a stepwise approach and getting really prepared for that next important step, which is that discussion with FDA next month.
Perfect. Thank you.
Thank you. Aisha [uncertain] , our next question comes from the line of Roger Song from Jefferies. Please go ahead.
Hey, good morning. Congrats on the progress, and thanks for taking our questions. This is Peter Chen calling in for Roger.
Hi, Peter.
Just a quick one for AUD from us. Are you still thinking of including lean patients in the AUD phase III? If so, have you guys observed a relationship between weight loss and heavy drinking day reduction in RECLAIM? Did patients with limited weight loss still show an alcohol benefit?
Yeah, so all our data, the totality of our data, allows us, and we confirmed this with our KOLs, that if in our phase II we had limited the BMI of the patients to patients above 25, now we will explore this in the phase III. So we will have a cohort of patients that are below 25 or normal into our cohorts, and we will be looking at this. With regard to our data, we are still looking at all these different aspects, but it is clearly there is a good response throughout the different BMI, and that is what allows us to include these patients below 25 or makes us comfortable and confident we can include them into the phase III program.
Great. Really appreciate the additional color. Thanks, guys.
Thank you.
Appreciate it.
Thank you. Aisha, our next question comes from the line of William Wood from B. Riley Securities. Please go ahead.
Thanks so much for taking our questions, and congrats on the continued progress here. Just to sort of double-click on PERFORMA execution, could you comment on how many patients have actually been randomized? In terms of sort of the mix between U.S. and ex-U.S., I believe you said that total sites activation will be around 300. Should we expect, is that 70 sort of maxing out in terms of the U.S., and then the rest should be ex-U.S.? Then I have a follow-up.
Yeah, so as I said earlier, we're focused on site activation in this phase while we enroll and start to dose patients. We're not yet at a point where we're going to comment on specific patient numbers. We have talked about that roughly one-third of the ultimate study sites will be in the U.S. So, with 70 in, there's some more to happen in the U.S., and again, that progresses really on a weekly basis in terms of adding those sites, and then the ex-U.S. would come next. Christophe, maybe any-
Yeah. No, I mean, this is exact. We are, as you understand, the phasing of those different sites will vary between countries. We have the vast majority of our sites already activated in the U.S., and this is really encouraging. We are moving step by step into the activations of the other countries. Europe, Asia, et cetera, will come next.
That will bring all these patients, again, to just repeat myself, but we're very encouraged when we see the screening, the number of patients that are coming through the sites right now by the PIs' engagement for the study, how they respond, and how they were present, and the receptions as well as the number of PIs and sites that have come to our booth at The Liver Meeting was also telling on that interest for the PERFORMA study. This is working. We are in the early stages, but this is working exactly as planned, and we see a great engagement to work with us.
Of course, we understand why this is such an important question, and we're thinking about it carefully as we move ahead. As I said, we'll provide the appropriate updates as the study matures, and I'm sure this will be a source of conversation on each quarterly call.
Got it. Also, for your AUD trial, obviously, we'll need to wait post end of phase II, and then the obviously appropriate timeline after that. Just in terms of what's your expectations on when we could actually expect the phase III to initiate? Is that something that could happen in the first half of next year? Also, based on your development already in MASH, should we expect a safety database, or should we expect the FDA to require a safety database for AUD or ALD? Maybe, are you already screening with PEth in your MASH trial? Thank you.
Christophe, take that question, then I'll come back on how to think about timing.
We are definitely using PEth in our PERFORMA MASH trials. This will be an important evaluation to be done. As we mentioned, pemvidutide has really the potential to treat both the appetites and the metabolic causes of the serious liver disease, as well as alcohol. We are looking at this into our phase III trial. For the AUD, there is a number of steps that we're taking to move forward, and we will include patients with also liver impairment or ALD in that population that do have AUD. This is where we're going right now and working with KOLs, with regulatory agencies to put all these aspects together.
This is a step-wise approach. We talked at the initial top-line readout that the next step was to compile the data, submit the data, get the meeting on the books with the FDA. That's the next step now in December. That will allow us, I think, to have a lot of the right inputs to finalize the design of the trial.
Then, of course, the funding question's going to be getting the right funding mechanism that we think is in ultimately the best interest of moving the program ahead and in the best interest of the shareholders. As I said earlier, we're not yet going to guide to timing around this. We'll update as we go through these steps. Underneath that is that kind of dual objective of trying to move as quickly as we can while also ensuring that each step of the process is the right thing for the program long term. Stay tuned on that.
Yeah. Just want to answer the question on the safety database. Obviously, with the number of patients, we already have exposed more than 750 patients. We expect to have those discussions with the regulators and trying to limit that safety database to its strict minimum on the specific AUD population and being able to use the other trials, like the MASH PERFORMA trials or the previous phase II trials for total exposure to the drug.
Very helpful. Appreciate it. Thank you very much.
Thanks.
Thank you. Our next question comes from the line of Patrick Trucchio from H.C. Wainwright & Co. Please go ahead.
Thanks. Good morning. Just a couple of questions. The first is, I was wondering how consistent was RECLAIM's drinking benefit across baseline BMI and weight loss subgroups, particularly among patients who maybe lost relatively little weight? Then I am wondering which AUD patient population offers the clearest initial commercial opportunity for pemvidutide based on the product profile that is emerging, and how the drug would be positioned among others in the space, particularly in Generics?
The data in the RECLAIM study were remarkably consistent between the different groups, with a response not only across different measures, as we have seen with the PROs and the more objective PEth measures, but also across subpopulations, gender, BMI, et cetera. The consistency is what makes those data extremely robust, and I will let Linda answer the questions on the commercial side.
Certainly. Thanks, Christophe. Thanks for the question. I think we have mentioned that of the 27 million people who meet the criteria in the U.S. for alcohol use disorder, there are roughly 12 million that suffer from or would meet the criteria for moderate to severe. And that is where we believe the chronicity of use, the binge drinking potential, et cetera, that leads to liver damage, they are the most likely to progress or, in fact, have subclinical underlying damage already that we believe having a direct-acting impact on the liver due to the glucagon is very important.
Not only do you have to reduce the drinking behavior, the drinking consumption, the amount of drinking, you also want to be protecting that liver and helping to heal that liver. And that is where the dual mechanism comes in and gives us an advantage that we believe will potentially play out in our clinical trials.
Great. Thanks so much.
Thanks, Patrick. Thank you, Patrick.
Thank you. Our next question comes from the line of Annabel Samimy from Stifel. Please go ahead.
Hi, this is Kyle on for Annabel. Thank you for taking our questions. Two from us. On the AUD primary, you guys selected WHO-RDL, and then the zero HDD as secondary. Just curious why you chose one over the other, and then how receptive that is from FDA. Separately on AUD, given that incretins are now 50% cash pay and semi-generic in early 2030s, how do you see your ability to price effectively, and do you envision cash pay and telehealth as a strong component of the commercial infrastructure? Thank you.
All right. Just as a reminder, both of those key secondary endpoints in our phase II study were highly statistically significant, the WHO-RDL and the no heavy drinking days. We believe that the WHO. We had the opportunity to choose any of them based on this. We chose, for right now, we're going to propose the WHO-RDL for a couple of reasons. One, the level of drinking and the risk of drinking is very relevant from an addictive aspect, and we believe that no heavy drinking days is a little less relevant from a clinical practice point of view.
At least this is what we are hearing from our experts, academic experts, or clinicians. This is a very relevant measure that risk is really important. It allows us also to look at the partial and full remission potentially for these patients in the phase III and move in this direction. This is an important one, and again, the results that we are seeing were very robust and very strong.
I will take the second part of that question. Recall that only about of all the AUD patients in meeting that criteria, only about 2.5% are receiving any kind of pharmacotherapy presently. Our data, as far as we are aware, is the strongest data in reduction of drinking and impact on AUD of any company that has presented to date. The uniqueness of, again, going directly to that liver issue and the tolerability of our product. This is something that patients may need to stay on for a while. We do not know. The tolerability is going to play in. All the features that we see coming from the inherent molecule matters in our whole presentation of 1-to-1, we believe will play into the value proposition for pemvidutide in AUD.
We are in conversations, we have had some early work talking to payers and some ad boards, and what would it take? How would that look? What would we need to show? What we need to demonstrate? I think we are well aware of how to approach that and the things that will be important. But clinically speaking, our data is very strong, and that is the kind of dual-action help that people will need potentially moving forward.
Okay, thank you.
Thank you. Our last question in the queue comes from the line of Andy Hsieh from William Blair. Please go ahead.
Thanks for taking our question. You talked about material overlap between AUD, ALD, and MASH. Regarding the effect size that we can expect to see from RESTORE reading out in the second half of next year, is that three to four kilopascal demonstrated from the IMPACT study a good metric to look at?
Thanks for the question. I cannot guide on the number here for what is happening in a population that we have not yet studied directly. We were really happy with the data that we have seen in our MASH with the three, almost four kilopascal in the population. That distinction was extremely strong. As a reminder, this is only at our middle dose, the 1.8 milligram dose. For the MASH trial, clearly this is very encouraging. For the ALD trial, again, if the effect is a number of consideration, you would have to assume that the effect is similar in both populations, that the timing of this effect is similar as well, all those kind of things.
This is why we think that having that study will be really important when we look at the AUD indications, because it will reinforce our filing package with a really good understanding around that ALD population. We already know that this is a population that is heavily drinking, so we will have the AUD population that is more the regular population, if you wish, but we will also be able to really focus on that liver impairment or ALD population. I think, clearly we are looking at the FibroScan, the VCTE, the change in kilopascal, as you are rightly saying. But so far, it sounds like the direct impact of glucagon on the liver, in addition to the impact of GLP-1 on the drinking levels, is really a big differentiation from the GLP-1 alone, especially in those severe and moderate patients.
All right. That is very helpful. Thank you.
Thank you.
Thank you. That concludes our Q&A session. At this time, I would like to turn the call back over to management for closing remarks.
Thanks a lot, operator, and thanks, everybody, for joining us today. As you heard on the call today, we remain confident in the opportunity ahead for Pemvi and the franchise that we are building around it. We have several important milestones ahead, so we remain focused on executing with speed, with efficiency, and advancing this differentiated therapy for patients with serious liver diseases and creating value for our shareholders. I will end the call with one overarching sentiment that should be the key takeaway, which is that our conviction in pemvidutide and its potential is stronger than ever as we look ahead. So, thanks again for joining us, and we look forward to updating you on our continued progress. Have a great day.
This concludes today's conference call. Thank you for participating. You may now disconnect.